Year: 2010

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Hypertension Core Curriculum

The Michigan National Kidney Foundation teamed up with the Michigan Department of Community Health to create a primer on hypertension for doctors, nurses and midlevel providers. The book just was finalized. The book is not copyrighted so I am able to upload it for people to use as they see fit.

I authored the subsection on lifestyle changes and blood pressure control.

Enjoy

Hypertension Core Curriculum

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The problem with the K/DOQI stages

In 2002 at the Spring Clinical Meeting of the National Kidney Foundation, K/DOQI released the Clinical Practice Guidelines for Chronic Kidney Disease Evaluation, Classification and Stratification.

These guidelines have become the dogma of CKD and all of my residents can accurately determine the CKD stage of their patients. The classifications have allowed epidemiologists to measure the burden of CKD. The crux of the guideline is that the severity of kidney disease is solely determined by the GFR.  This is helpful in determining where the patient has been but it is not good at determining where patients are headed.

In some ways, it is a negative prognostic tool, people with worse stages of CKD actually have better outcomes and vice versa.

To understand how this works one needs to understand how we calculate the GFR. The accepted equation was created by Levey et al using the MDRD data base. Levey AS, Greene T, Kusek JW, Beck GJ: A simplified equation to predict glomerular filtration rate from serum creatinine. J Am Soc Nephrol 11:A0828, 2000 (abstract)

GFR=186 x sCr -1.154 x Age -0.203 x (0.742 if female) x (1.212 African-American)

African Americans, for the same creatinine, are given a 21% increase in their GFR and women lose 26%. If GFR provided prognostic information one would think that African Americans were protected from chronic kidney disease and women were at higher risk. Yet that is not the case. African Americans have the highest rates of ESRD, 998 per million compared to 273 for white Americans: (USRDS 2009 Annual Data Reports, NIH, NIDDK, Bethesda, MD, 2009.)

The lifetime risk of ESRD is 1 in 50 for woman and 1 in 40 for men (Kiberd BA, Clase CM. JASN 13: 1635-44, 2002).

The negative exponent on the age variable means that as one ages their GFR falls. The problem is that the risk for ESRD appears to fall, likely because of the competing endpoint, death. This was best shown in a 10 year study by Erikson and Ingebretsen. They showed that as patients aged they were more and more likely to die and less likely to develop ESRD.
I do not doubt that the MDRD eGFR is a good measure of renal function I am frustrated by the way it is used to frame management decisions.
Its like the nephrologists in the K/DOQI work group looked at the framework established in oncology and adopted a staging system but did not consider the importance of the grading system. Not all CKD stage threes are alike, some patients have more aggressive disease than others and this needs to be addressed in our clinical practice guidelines.                                                            
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Best urine quotation

“What is man, when you come to think upon him, but a minutely set, ingenious machine for turning with infininite artfulness, the red wine of Shiraz into urine?”

Isak Dineson, Danish author (1885-1962)

I first heard this quotation from my mentor Adrian Katz. Only Adrian would compare the wine you were currently drinking to urine. 
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How I used my newly acquired PubMed skills

Yesterday I gave one of my favorite lectures, Renal Adventures in Imaging.

After I finished the lecture I spent some minutes playing with my new skills on PubMed and found this article: N-acetylcysteine effect on serum creatinine and cystatin C levels in CKD patients that completely goes against one of the figures and points of my newly scribed chapter:

[The inability of acetylcysteine to prevent dialysis or mortality] maybe because acetylcysteine alters creatinine handling in the proximal tubule. Acetylcysteine, actually accelerates the excretion of creatinine resulting in decreased serum creatinine.

After Tepel published his original work on acetylcysteine in 2000 everyone went a little crazy drinking the Mucomyst cool-aid. Here was a cheap, safe and already approved, remedy to the pervasive problem of contrast nephropathy. Everyone was so drunk with the excitement that they didn’t note that the 85% reduction in contrast nephropathy was not associated with a reduction in the need for acute dialysis or a reduction in patient morbidity and mortality.

In 2004, Hoffmann Et al. published the above quoted article which showed a modest but significant reduction in serum creatinine following ingestion of acetylcysteine. This seemed to me to be the best explanation for why a therapy could prevent an increase in creatinine but not prevent dialysis. (Data on the lack of prevention of dialysis from Miner et al. Am Heart J 2004.)

Apparently the patron saint of contrast nephropathy, Richard Solomon, recently reevaluated this theory and found it lacking. He took 30 patients with GFR < 60 mL/min and given 1,200 mg of acetylcysteine every 12 hours for four doses. Creatinine and cystatin C were measured at baseline, 4 and 48 hours after the last dose of acetylcysteine. They found:

Serum creatinine and cystatin C levels did not change significantly at either 4 h or 48 h following the last dose of NAC compared with the baseline values (Table 2; Figures 1 and 2). However, a small but statistically significant reduction in the ratio of serum creatinine to cystatin C was observed at 4 h but not 48 h.

click to enlarge
Solomon postulates that in patients with chronic kidney disease (a population that better represents the people who actually are given contrast nephropathy prophylaxis) the proximal tubule secretion of creatinine may already be maximized so that it cannot be further upregulated by acetylcysteine.
The end result is that changes in creatinine found during acetylcysteine administration likely represent changes in GFR and are not merely artifactual.
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Noon conference St John Macomb: Renal Adventures in Imaging

Yesterday I gave one of my favorite lectures, Renal Adventures in Imaging.
It is a lecture on three issues in nephrology that are not normally put together in a single lecture:
  1. Phosphate nephropathy
  2. Nephrogenic fibrosing dermopathy (I’ll never get used to calling it nephrogenic systemic fibrosis because, despite what the literature states, all five patients I have seen had purely dermatologic manifestations)
  3. Contrast nephropathy
I like the lecture because it is not a typical nephrology lecture. 
I gave the lecture Seder-style and had crammed for the last three days getting the booklet ready. It’s the longest booklet by one sheet (32 pages rather than my standard 28). It turned out pretty good, though the acetylcysteine section needs to be built up and I need to comb through it for typos.
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Just spent 15 minutes getting better at PubMed

This is time that will pay major dividends down the road.

The mayo clinic libraries have posted a series of screencasts that will make you better at PubMed. Spend the time.

https://videopress.com/v/wp-content/plugins/video/flvplayer.swf?ver=1.18

https://videopress.com/v/wp-content/plugins/video/flvplayer.swf?ver=1.18

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iPad: the delivery on a 14 year old pledge

In 1996, a year before returning to Apple, Fortune interviewed Steve Jobs. When asked what he would do to save Apple he explained:

If I were running Apple, I would milk the Macintosh for all it’s worth — and get busy on the next great thing. The PC wars are over. Done. Microsoft won a long time ago.

At that time, this quote was like a dagger in my heart. At the time Apple was flailing. Windows was rocking and the drumbeat of the end was getting louder. To hear the creator of the Mac declaring the war lost was heart breaking. I chalked it up to an off-the-cuff, spoiled-grape quotation.

Later, after Steve came back to Apple I began to feel vindicated in my opinion. Steve didn’t act like he was “milking the Macintosh.” In no way could I see his actions as just “milking the Mac.” Check out this video of Steve at the 1997 MacWorld. I see no indication of the hopelessness that the PC wars were over (Steve enters at 5:30):

So from the moment Steve re-enters the PC picture, he restokes the PC wars. He introduces the iMac. He successfully recreates the NeXT operating system as OS X. And, though he had phenomenal success growing Apple’s computer business, none of that really fits the bill of The Next Insanely Great Thing.

When the iPod came out in late 2001 I wondered if this was the next great thing, but music, no matter how cool, was just too small a stage for the man who had twice revolutionized computers. Also when you look at the history of the iPod it wasn’t an Apple idea, rather, the concept was brought to Apple by Steve Fadell after Real passed on it. It didn’t feel like what steve meant by “getting busy on the next great thing.”
What the iPod did do, is demonstrate that Apple could win in consumer electronics. This time after Apple innovated the followers at Sony, Microsoft and Dell couldn’t overtake’em. The disaster which nearly destroyed Apple in the PC wars wasn’t re-run during the digital music revolution. Apple invented the digital music business and ten years later the story is still only about Apple.

When the iPhone was introduced this felt like the The Next Big Thing. Phones are ubiquitous and important. The shift to mobile computing has been a long standing theme in the computer industry. Smart Phones aren’t just about smarter phones but putting the power of the computer in your pocket. So it was clear that the iPhone fit the bill of the “the next great thing” but what wasn’t clear was that it would replace the Macintosh. 
With the introduction of the iPad I am now convinced that it will replace the Mac. The two pieces of data that convinced me of this was the demonstration of the iWork for iPad and the support for real keyboards. Both of those mean that the iPad is not just a media consumption device but also a media creation device. Congratulations Steve, I hope the iPad represents the next revolution in computing.
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Marathon running is bad for your heart? Say it isn’t so!

I am an avid recreational runner. I am just about to come up on my 2 year anniversary of being a pretty regular runner, see Operation: Marathon. So it was pretty disturbing to see these two abstracts getting press form the 2010 American College of Cardiology:

  1. Researchers have shown that long-term marathon runners, those who have completed at least 25 marathons over the past 25 years, have increased coronary calcium and calcified plaque volume.
  2. A second group did a study which suggested that marathon runners had increased aortic stiffness compared with individuals who exercised recreationally
I would really like to stress that both of these studies do not look at patient oriented endpoints but intermediate end-points. I would hesitate to turn anyone off of exercise, which I tell my patients is the closest thing we have to a fountain of youth, until we had data containing hard end-points.
To corroborate that, the first study looked at a number of other cardiovascular risk factors, and all of these pointed to improved cardiovascular risk profiles:
  • lower heart rate
  • lower body weight
  • lower BMI
  • Higher HDL-cholesterol levels
The press release is at this link, but you will need to register to get to the meat.
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Aldosterone escape versus Aldosterone breakthrough

Fluid and electrolyte deity, Robert Schrier,  had an interesting editorial in Feburary’s Nature Reviews: Nephrology (yes, I’ve gotten a little behind in this blogging business).

Escape versus breakthrough refere to completely different and unrelated concepts related to aldosterone.

  • Aldosterone breakthrough occurs following administration of an ACEi or ARB. ACEi block the conversion of angiotensin I to angiotensin II. The decrease in angiotensin II lowers aldosterone. Angiotensin receptor blockers prevent angiotensis II from from binding receptors through out the vasculature but including the adrenal gland where it prevents aldosterone release. At least that is the plan. In reality about 30-40% of patients given ACEi or ARBs have only a temporary decrease in aldosterone and then after a few weeks, aldosterone returns to pre-treatment levels.  

  • Aldosterone escape is a physiologic phenomenon that occurs with hyperaldosteronism. Aldosterone initially decreases urinary sodium increasing sodium retension contributing to hypertension. This does not result in edema because the sodium retention is short lived. After a short time urinary sodium returns to normal through a process called aldosterone escape. There are two processes that account for this:

    1. Pressure natriuresis. Increased blood pressure decreases distal sodium resorption. The exact mechanism of pressure natriuresis is unknown, it is thought to be mediated by hydrostatic forces. Increased blood pressure is transmitted to the peritubular capillaries, so the resorption of solutes must overcome an elevated hydrostatic pressure gradient. In the face of this increased gradient, sodium resorption falls.
    2. Decreased proximal sodium resorption. Volume expansion decreases proximal sodium reabsorption and increases sodium delivery to the distal nephron and overwelms the aldosterone induced sodium resorption.

The implications of aldosterone escape is that primary hyperaldosteronism does not cause edema. It also explains the delay in hypokalemia found with primary hyperaldosteronism. Aldosterone stimulates potassium excretion but hypokalemia is a late finding in primary hyperaldosteronism. The increased potassium excretion occurs with aldosterone escape when the increased sodium delivery (decreased proximal absorption, i.e. escape) occurs with the increased aldosterone levels.

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Unmatch Day 2010

The worst day in medical school. If you don’t match you get contacted that you need to scramble for a spot. ugghh. Scramble starts tomorrow at noon. Its high stake musical chairs. Hope everyone finds a seat. 
Best day of med school just around the corner on March 18th at noon EDT.

Are any PBfluid readers fourth year med students? Where did you match? Leave a comment.